Cancer cells exhibit slightly elevated levels of reactive oxygen species (ROS) compared with normal cells, and approximately 90% of intracellular ROS is produced in mitochondria. In situ mitochondrial ROS amplification is a promising strategy to enhance cancer therapy. Here we report cancer cell and mitochondria dual-targeting polyprodrug nanoreactors (DT-PNs) covalently tethered with a high content of repeating camptothecin (CPT) units, which release initial free CPT in the presence of endogenous mitochondrial ROS (mtROS). The in situ released CPT acts as a cellular respiration inhibitor, inducing mtROS upregulation, thus achieving subsequent self-circulation of CPT release and mtROS burst. This mtROS amplification endows long-term high oxidative stress to induce cancer cell apoptosis. This current strategy of endogenously activated mtROS amplification for enhanced chemodynamic therapy overcomes the short lifespan and action range of ROS, avoids the penetration limitation of exogenous light in photodynamic therapy, and is promising for theranostics.

与正常细胞相比，癌细胞的活性氧 (ROS) 水平略有升高，并且大约 90% 的细胞内 ROS 是在线粒体中产生的。原位线粒体 ROS 扩增是增强癌症治疗的一种有前景的策略。在这里，我们报道了癌细胞和线粒体双靶向聚前体药物纳米反应器（DT-PN）与高含量的重复喜树碱（CPT）单元共价连接，在内源性线粒体ROS（mtROS）存在的情况下释放初始游离CPT。原位释放的CPT作为细胞呼吸抑制剂，诱导mtROS上调，从而实现CPT释放和mtROS爆发的后续自循环。这种 mtROS 扩增赋予长期高氧化应激，诱导癌细胞凋亡。目前这种内源性激活的mtROS扩增增强化学动力学治疗的策略克服了ROS寿命短和作用范围短的问题，避免了光动力治疗中外源光的穿透限制，并且在治疗诊断学方面具有广阔的前景。